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Helical CT Scans and Lung Cancer Screening

Lung cancer is the foremost cause of death from cancer in the United States, leading to nearly 160,000 deaths in 2006 (USCS). Annually, nearly 200,000 people have a new diagnosis of lung cancer (See related blog on new Surgeon General Report).

Efforts to develop methods to detect the cancer early enough to improve survival of the diagnosed persons have been largely unsuccessful. A recent study of a relatively new form of screening using helical computerized tomography (CT) demonstrated fewer lung cancer deaths among individuals at high risk of lung cancer who received this screening than among a similar group screened with chest radiography (chest x-rays or CXRs). There is great interest in this finding, and there is hope that this might provide new approaches to cancer screening among workers with increased risk for lung cancer because of past occupational exposures.

NIOSH researchers are in contact with the investigators who conducted the study and will learn more from them when the findings are published in the spring of 2011. This blog provides some background information on the study and describes the approach that NIOSH will take in considering what the findings mean for worker screening.

The National Lung Screening Trial

In September 2002, the National Cancer Institute (NCI) launched the National Lung Screening Trial (NLST) to compare the effects of two screening procedures, low-dose helical CT and chest x-ray, in reducing lung cancer mortality in current and former heavy smokers aged 55 to 74. The NLST was a national randomized controlled trial in which 53,454 participants were randomly assigned to one of two groups—chest x-ray or low-dose helical CT—and received annual screenings based on their assignment for three years. The groups were then followed for five years beyond the final screening. (Available at http://radiology.rsna.org/content/early/2010/10/28/radiol.10091808)

The primary scientific goal of the NLST was to determine whether three annual screenings with low-dose helical CT would lead to earlier detection and reduced mortality from lung cancer relative to screening with CXR. The secondary endpoint of the NLST was a decrease in deaths from all causes.

On November 4, 2010, the NCI released to the press that NLST researchers had found, in interim analyses, 20.3% fewer lung cancer deaths among those who were screened with low-dose helical CT compared with those who were screened with chest x-rays.

Further, preliminary results showed that among individuals screened with CT, 24.2% had a finding that could indicate the presence of a lung cancer (“positive screen”). In contrast, 6.9% of those screened with CXR had such a finding. CT screening detected 649 cancers out of 18,149 positive screens (3.6%) while CXR screening detected 279 cancers out of the 5,044 positive screens (5.5%). Not all lung cancers were detected by the screening process.

Key Points to Consider

It is important to emphasize that the data derived from the NLST was obtained from a very specific population group—individuals at high risk for developing lung cancer due to present or past heavy smoking, aged 55 to 74, and do not necessarily apply to the general population or specific populations of workers.

Screening with CT scans is not risk-free. Radiation exposure from repeated CT scans is cumulative and can lead to illness, including cancer. While a “low-dose” method was used, this is relative to a full diagnostic helical CT scan (average radiation effective dose 7 mSv) (Mettler 2008). The radiation dose for this “low-dose” method (1.5 mSv in the NLST) is about 15 times higher than a CXR (average effective dose 0.1 mSv) (Mettler 2008). The screening process itself can generate suspicious findings that turn out not to be cancer in the vast majority of cases, producing significant anxiety and expense (similar to the recent mammography debate). Furthermore, people who receive false-positive results may be subjected to unnecessary testing, invasive diagnostic and surgical procedures and complications. In the NSLT it appears that only 3.6% of positive CT screens were related to a lung cancer, while 96.4% of the positive screens were not (false positives).

Consideration of the use of any screening test in occupationally exposed groups requires a careful assessment of the risk of a given condition. There are a number of agents associated with occupational lung cancer. However, the excess risks for lung cancer associated with these occupational exposures vary depending on the actual exposures; it will be important to evaluate and compare the excess lung cancer risks from occupational exposures with the excess lung cancer risk from heavy cigarette smoking. The risk of lung cancer from a specific exposure will directly affect the likelihood that a positive screening test for lung cancer will actually be evidence that the cancer exists. In other words, high risk for lung cancer in the NSLT trial (because all participants were heavy smokers for many years) made it more likely that a “positive” finding on a CT scan was in fact a lung cancer.

Future Work

The NLST investigators are conducting more comprehensive analyses to assess adverse events related to the screening; as well as healthcare utilization for all reasons related to the acquisition of the images, and quality of life and cost-effectiveness endpoints. They will be publishing their peer-reviewed findings in the early spring of 2011. NIOSH will consider these findings carefully, consult further with the NCI investigators, and work with stakeholders in labor, industry, and the occupational medicine clinical community to consider the meaning of these findings for workers potentially at risk for lung cancer because of occupational exposures.

Dr. Tramma is a Senior Service Fellow/Medical Officer in the Surveillance Branch of the NIOSH Division of Respiratory Disease Studies.

Dr. Storey is Chief of the Surveillance Branch in the NIOSH Division of Respiratory Disease Studies.

Dr. Trout is Associate Director for Science in the NIOSH Division of Surveillance, Hazard Evaluations, and Field Studies.

Dr. Sweeney is Chief of the Surveillance Branch in the NIOSH Division of Surveillance, Hazard Evaluations, and Field Studies.

U.S. Cancer Statistics Working Group. United States Cancer Statistics: 19992006 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2010. Available at: http://www.cdc.gov/uscs

4 comments on “Helical CT Scans and Lung Cancer Screening”

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These findings are a definite step forward to improve the mortality from lung cancer. The detection of lung cancer by low dose helical CT is similar to the MRI “story” in breast cancer. These advances are costly in terms of expense, angst, and increase in number of biopsies, but lives are being saved. The increased work for such modest gains makes one even more vigilant to help and support smokers to quit smoking.

It is excellent that NIOSH is paying close attention to this issue. A few comments:

1.The NIOSH comment should point out that the NCI RCT preliminary results found a 20% reduction in lung cancer mortality. That is the single most important preliminary result of the NCI study and summarizes the magnitude of the potential benefit.
2.NIOSH estimated that there were 10,000-27,000 occupational lung cancer deaths in the U.S. in 1997 (Steenland et al AJIM 2003), a fact that assists in understanding the magnitude of the potential benefit.
3.Brenner estimated that radiation-related lung cancer risk from 25 years of annual low dose chest CT to a 50 year-old woman was <1% increase in lifetime lung cancer risk (Brenner Radiology 2004). To calculate the estimate, he used a 60 mAs CT tube current setting, which is twice that currently in use in low dose chest CT lung cancer screening programs. The radiation-related risk of low dose chest CT scanning appears to be low.
4.In any discussion of the problem of "false positive" low dose chest CT scans, a crucial distinction in "positivity" of chest CT scans must be made. In <2% of chest CT scans, a suspicious lesion is seen by the radiologist and requires careful immediate work-up. Most "positive" chest CT scans, however, have indeterminate lung nodules that are readily managed with a repeat low dose chest CT at 3 or 6 months after the initial CT scan. Few of these lung nodules change at the 3 or 6 month scan, but the few that do are sent for further clinical attention (Markowitz et al Chest 2007). The NLST of NCI did not include the 3 or 6 month follow-up scan as part of the program, but it has been routinely used as part of the I-ELCAP protocol. This protocol feature will greatly help to avoid unnecessary testing.Disclosure: Dr. Markowitz is funded by the Department of Energy to conduct low dose chest CT scanning of nuclear weapons workers. He has provided medico-legal expertise on this topic in 2 lawsuits.

On re-reading my comment sent yesterday, I have two corrections. In fact, the NIOSH comment did cite the 20% lung cancer mortality reduction. Also Steenland and NIOSH colleagues estimated that 10,000 to 20,000 lung cancer were caused by occupational agents in 1997 (Steenland et al. AJIM 2003.

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